Suppression of feeding, drinking, and locomotion by a cannabinoid receptor “silent antagonist”

Abstract: This study compared the effects of the putative cannabinoid receptor ‘silent antagonist’ O-2050 with the cannabinoid receptor inverse agonist SR 141716 on food and water consumption, and locomotor activity. Non-deprived male Wistar rats were habituated to the apparatus and testing procedures, then injected intraperitoneally with vehicle, O-2050 (0.03-3.0 mg/kg), or SR 141716 (3.0 mg/kg) prior to 4-h test sessions. Food consumption was significantly reduced by both drugs. Water intake and locomotor activity were significantly reduced only by O-2050. Results support the notion that cannabinoid receptor antagonists suppress feeding behaviour by blocking an endogenous cannabinoid orexigenic signal, rather than by inverse agonism at cannabinoid receptors. However, further studies are needed to confirm the status of O-2050 as a cannabinoid CB1 receptor antagonist devoid of inverse agonist properties.